Visual and radiographic contrast media and method of use



United States Patent 3,196,!230 VESUAL AND RADTGGRAPHTC CONTRAST MEDTAAND METHGD OF USE Nichoias G. Demy, 527 Foothil' Road, Semerville, Nu l.No Drawing. Filed Feb. 6, 1963, Ser. No. 256,533 3 Claims. (Cl, rs7 9sThe present invention relates to a liquid radiographic contrast mediumand more particularly to a distinctively colored iodinated oilysubstance, for example, an iodinated fatty acid, which exhibits markedradiographic opacity and yet is clearly distinguishable from aqueousbody fluids when observed using ordinary light in the visible portion ofthe spectrum.

More specifically, the invention relates to a distinctively colored,radiopaque, oily liquid suitable for injection into various cavities ofthe human body for purposes of fluoroscopic and radiographicexamination, the liquid being subsequently Withdrawn after completion ofthe examination. During the withdrawal, which preferably takes placeunder ordinary light without X-rays, the distinctive color of the liquidand its oily consistency permit the examiner to determine with certaintywhen the liquid being withdrawn from the body cavity ceases to containthe iodinated substance and thus to ascertain when substantially all ofthe contrast medium has been removed.

Suitable colorless contrast mediums are, for example, fatty acidsdescribed in Strain et al., US. Patent No. 2,348,231, issued May 9,1944.

The distinctively colored iodinated fatty acid solution of the inventionis suitable for use in myelography; positive contrast ventriculography;lymphangiography; and radiography of the sinus tracts, fistulouscommunications, ducts and other body cavities.

In general, solutions embodying the invention are prepared by theaddition of a fat soluble chromophore to the common esters of iodinatedphenyl aliphatic acids. The chromophoric group may be D & C Green #6(Quinizarin Green SS) having the chemical name of 1,4- bis (p-toluino)anthraquinone; or D & C Violet #2 (Alizurol Purple or D & C Blue #3)having the chemical formula of l hydroxy-4-p-toluionoanthraquinone; or anon-toxic metallic salt of alkannin, G T-1 0 The preferred iodinatedfatty acid which serves as the vehicle for the chromophore is a mixtureof the esters of ethyl iodophenylundecylic acids having a specificgravity materially in excess of unity and more particularly having theformula of and the preferred chromophore is Quinizarin Green SS havingthe chemical name of 1,4-bis (p-toluino) anthraquinone.

For example, one gram of Quinizarin Green SS is added to 100 grams ofthe ethyl ester of iodophenylundecylic acid. This results in a stabledeep green-blue water immiscible, non-emulsifying, freely-flowing fluidwhich does not stain the body fluids or tissues. The solution contrastssharply on a radiographic film and during fluoroscopic observation; atthe same time, it is clearly visible under ordinary illumination to theunaided eye or the dark-adapted eye covered by red goggles as a deepgreen-blue oily layer which underlies and is readily distinquished fromthe colorless, a ueous spinal fluid.

The radiopaque oily solution consists essentially of a dye and aradiopaque vehicle, both of which have proven to be internallyacceptable by the body and both of which are well known to be nontoxic.The Quinizarin Green SS is dissolved within the oily iodinated fattyacid without any accompanying chemical reaction forming a diffli hfidfiPatented July 26, 1965 ice ferent compound. The resulting solution isinjectionally acceptable to the human body and its cavities.

Although other nontoxic coloring agents may be used wherein the color isreadily distinguishable from the colors of the fluids of the human body,a color in the blue end of the visible portion of the spectrum isessential when the medium is being withdrawn. While the radiographicphotography may be performed in a fully lighted room, the fiuoroscopy isperformed in a darkened room and the examiner wears goggles with lensesformed of red-colored glass. The deep green-blue color of the radiopaquefatty acid makes it unnecessary for the examiner to remove the redgoggles for observation and volumetric evaluation of the liquid beingwithdrawn from the body cavity which has been examined and thus destroythe dark adaptation of his eyes.

The method of myelography will be described as an example of thelimitations which the current medium now imposes on the examination.Generally, from three to twelve cubic centimeters of the colorlessradiopaque medium are injected through a long needle into the spinalcanal. The location of the injected oily contrast medium is thenobserved fluoroscopically and the patient assumes a position such thatthe contrast medium flows by gravity into the region of the spinal canalwhere the abnormality is suspected. X-ray pictures are taken. The needleremains in place while the pictures are being taken and developed.

When the desired fluoroscopic and photographic information has beenobtained, attempt is made to withdraw as much of the injected materialas possible using a syringe connected to the needle. The conventionalcontrast medium is a colorless liquid immiscible with the spinal fluidand will hereinafter be designated as oil.

7 This oil may become slightly emulsified or dispersed into smallglobules when mixed with air and spinal fluid drawn into the syringe.This makes it diflicult to distinguish between the spinal fluid and theoil during withdrawal into the syringe and also makes it difiicult toestimate the amount of oil withdrawn. Time is lost in crude andcumbersome testing for oil, and in uncertain estimation of the amountrecovered from the spinal canal. During this time, the examiners eyesare covered with red goggles to preserve dark adaptation for thefluoroscopic identification, positioning and removal of the oil.Excessive spinal fluid is lost and manipulation of the needle in thespinal canal can be extremely uncomfortable to the patient. Patientsrefuse to have the examination repeated and physicians are reluctant toperform the examination even initially because of these technicaldifficulties. Often the attempt to remove the oil is abandoned infrustration and significant amounts remain behind.

The remaining oil which has not been removed is very slowly absorbed andresidues are often seen on X-rays of the spinal column ten or more yearsafter the examination. This residual oil can be a source of gravediagnostic error during the lifetime of the patient if radioactiveiodine uptake studies o r" the thyroid gland are attempted later.

For a more detailed description of myelography using uncolored contrastmedia and the problems involved, reference may be had to a bookentitled, Myelography, by Robert Shapiro, M.D., Yearbook MedicalPublishers, Inc., Chicago, 1962, Library of Congress Catalog Card No.62-11257. Chapter 4 is particularly relevant.

The green-blue color of the injectionally acceptable oily contrastmedium described above avoids many disadvantages of an uncoloredcontrast medium. Because of the distinctive color, the amount ofcontrast medium may easily be measured with accuracy and the amountwhich remains within the patients body is readily and accuratelyascertainable. This enables the neurosurgeon, orthoisease pedist orradiologist to tell whether he is withdrawing spinal fluid or contrastmedium into the syringe; it technically facilitates the operativeprocedure and spares the patient discomfort and pain; it preventsexcessive loss of spinal fluid; it makes possible the use of 10 to 30cubic centimeters of contrast medium instead of 3 to 12, thus improvingdiagnostic accuracy by outlining a greater length of spinal canal; andit decreases the time of the fluoroscopic examination. Most important ofall, it facilitates removal of most, if not all, of the oily contrastmedium and thus prevents later confusion if radioactive iodine is to beused in the diagnosis of thyroid gland disease. Any of the residualdistinctively colored oil can be identified and removed by theorthopedist or the neurosurgeon if an operation on the spinal canalshould be performed at a later date.

' Heretofore, the entire ventricular system of the brain has beenexamined by injection of air because the large volume of the ventriclesprecluded the use of a liquid medium whichpwould be difiicult to remove.With the useof an easily identifiable colored medium, positive contrastof ventriculography becomes a feasible examination.

In lymphangiography, regional lymph nodes which are the seat of primaryor metastatic tumors, after X-ray examination using the colored oil,become visibly pigmented, thus enabling the surgeon to find and removethese tumors after preliminary identification on the X-ray film.

In the examination of fistulae, sinuses, ducts and cavities, thediseased or abnormal tracts may first be studied using X-rays inconjunction with the colored radiopaque oil described above. Bypermitting a certain amount of the colored oil to remain, the affectedtracts which appear in the X-ray film may be visually identified withprecision during the course of a correctional operation.

Reference is made to Tainter and Grayson: Radiopaque Diagnostic Agents,Annals of the New York Academy of Science, volume 78, art. 3, page 965(Summary). July 2, 1959, stating on authority:

The medicolegal implications of residual dye are frightening. From themedical viewpoint residues of this 'dye (Pantopaque) preclude the use ofradioactive tracer studies for the lifetime of the patient. A new radio-I graphic agent for myelography is urgently needed.

g I I- CHOHQ(CHZ)GCHZOOOOHZCH3 having about 1% by weight of a coloringagent dissolved therein, said coloring agent being selected from thegroup consisting of: 1,4-bis (p-toluino) anthraquinone;1-hydroxy-4-p-toluino anthraquinone; and a metallic salt of alkannin, CI-1 0 2. A radiographic contrast medium consisting essentially of havingabout 1% by weight of 1,4-bis (p-toluino) anthraquinone dissolvedtherein.

3. A radiographic contrast medium consisting essen tially of havingabout 1% by weight of l-hydroxy-4-p-toluino anthraquinone dissolvedtherein.

References Cited by the Examiner UNITED STATES PATENTS 1/43 Bell et al167-95 OTHER REFERENCES Tainter et al., Annals of the New York Academyof Sciences, vol. 78, article 3, pp. 956 and 958, July 2, 1959.

LEWIS GOTTS, Primary Examiner.

FRANK CACCIAPAGLIA, JR., Examiner.

1. A RADIOGRAPHIC CONTRACT MEDIUM CONSISTING ESSENTIALLY OFI-(1,4-PHENYLENE)-CH(-CH3)-CH2-(CH2)6-O-O-O-CH2-CH3 HAVING ABOUT 1% BYWEIGHT OF A COLORING AGENT DISSOLVED THEREIN, SAID COLORING AGENT BEINGSELECTED FROM THE GROUP CONSISTING OF: 1-4 BIS (P-TOLUNO) ANTHRAQUINONE;1-HYDROXY-4-P-TOLUINO ANTHRAQUINONE; AND A METALLIC SALT OF ALKANNIN,C16H10O5.